Evidence map›Paper›PMID 35476528›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2022

Dromedary camel nanobodies broadly neutralize SARS-CoV-2 variants.

Jessica Hong, Hyung Joon Kwon, Raul Cachau, Catherine Z Chen, Kevin John Butay, Zhijian Duan, Dan Li, Hua Ren, Tianyuzhou Liang, Jianghai Zhu and 8 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 2 pooled it
3.7field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.

  1. Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023
    Pooled it
  2. Pooled it
  3. Review
  4. Nanobodies targeting SARS-CoV-2 variants.Acta pharmaceutica Sinica. B · 2026
    Review
  5. Decoding antibody response to MERS-CoV in wild dromedary camels.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Article
  7. Article
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  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Outsmarting Pathogens with Antibody Engineering.Annual review of chemical and biomolecular engineering · 2023
    Review
  18. Identification of nurse shark VFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 10 institutions in 1 country.

Jessica HongLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20891.
Hyung Joon KwonDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993.ORCID 0000-0001-7846-8779
Raul CachauData Science and Information Technology Program, Leidos Biomedical Research, Inc., Frederick, MD 21702.
Catherine Z ChenNational Center for Advancing Translational Sciences, NIH, Rockville, MD 20850.ORCID 0000-0002-6900-6553
Kevin John ButayMolecular Microscopy Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Zhijian DuanAntibody Engineering Program, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20891.
Dan LiLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20891.
Hua RenLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20891.
Tianyuzhou LiangLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20891.
Jianghai ZhuData Science and Information Technology Program, Leidos Biomedical Research, Inc., Frederick, MD 21702.
Venkata P DandeyMolecular Microscopy Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Negin P MartinViral Vector Core, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.ORCID 0000-0003-3166-8989
Dominic EspositoProtein Expression Laboratory, NCI RAS Initiative, Frederick National Laboratory for Cancer Research, Frederick, MD 21702.ORCID 0000-0002-9987-1687
Uriel Ortega-RodriguezDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993.
Miao XuNational Center for Advancing Translational Sciences, NIH, Rockville, MD 20850.
Mario J BorgniaMolecular Microscopy Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.ORCID 0000-0001-9159-1413
Hang XieDivision of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, MD 20993.ORCID 0000-0001-8318-5554
Mitchell HoLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20891.ORCID 0000-0002-9152-5405
National Cancer Institute · USNational Institute of Environmental Health Sciences · USCenter for Biologics Evaluation and Research · USCenter for Cancer Research · USNational Center for Advancing Translational Sciences · USLeidos Biomedical Research Inc. (United States)Leidos (United States) · USProtein Express (United States) · USTriangle · USUnited States Food and Drug Administration · US

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
Development of new antibody-based cancer therapiesZIABC010891 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HO, MITCHELL · 2009 to 2025
$21.4M
Viral Vector CoreZICES102506 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI MARTIN, NEGIN · 2009 to 2025
$18.4M
Antibody Engineering ProgramZICBC011891 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HO, MITCHELL · 2019 to 2025
$4.5M
Epitope dynamics of SARS-CoV-2 S protein by cryo-electron tomography and single particle cryo-EMZIAES103341 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI BORGNIA, MARIO · 2020 to 2025
$3.9M
Development of a Robust Bioprocess to Rapidly Produce Griffithsin, a Broad-Spectrum Therapeutic and Preventive Antiviral CandidateZIATR000441 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI WU, EDWARD · 2022 to 2025
$1.1M
Development of neutralizing nanobodies against SARS-CoV-2ZIABC011943 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HO, MITCHELL · 2020 to 2023
$774k
Antibody Therapy of CancerZ01BC010891 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HO, MITCHELL · 2008 to 2008
$56k
Intramural NIH HHS Z01 BC010891Intramural NIH HHS ZIA BC010891Intramural NIH HHS ZIA BC011943Intramural NIH HHS ZIA ES103341Intramural NIH HHS ZIC BC011891NCI NIH HHS 75N91019D00024
6 · The paper itself

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike is a trimer of S1/S2 heterodimers with three receptor-binding domains (RBDs) at the S1 subunit for human angiotensin-converting enzyme 2 (hACE2). Due to their small size, nanobodies can recognize protein cavities that are not accessible to conventional antibodies. To isolate high-affinity nanobodies, large libraries with great diversity are highly desirable. Dromedary camels (Camelus dromedarius) are natural reservoirs of coronaviruses like Middle East respiratory syndrome CoV (MERS-CoV) that are transmitted to humans. Here, we built large dromedary camel VHH phage libraries to isolate nanobodies that broadly neutralize SARS-CoV-2 variants. We isolated two VHH nanobodies, NCI-CoV-7A3 (7A3) and NCI-CoV-8A2 (8A2), which have a high affinity for the RBD via targeting nonoverlapping epitopes and show broad neutralization activity against SARS-CoV-2 and its emerging variants of concern. Cryoelectron microscopy (cryo-EM) complex structures revealed that 8A2 binds the RBD in its up mode with a long CDR3 loop directly involved in the ACE2 binding residues and that 7A3 targets a deeply buried region that uniquely extends from the S1 subunit to the apex of the S2 subunit regardless of the conformational state of the RBD. At a dose of ≥5 mg/kg, 7A3 efficiently protected transgenic mice expressing hACE2 from the lethal challenge of variants B.1.351 or B.1.617.2, suggesting its therapeutic use against COVID-19 variants. The dromedary camel VHH phage libraries could be helpful as a unique platform ready for quickly isolating potent nanobodies against future emerging viruses.

Indexed as

COVID-19Single-Domain AntibodiesAnimalsCamelusHumansMiceSARS-CoV-2Single-Domain Antibodiescryo-EMdromedary camel nanobody VHHneutralizing antibodySARS-CoV-2single-domain antibody

Identifiers

PMID35476528
PMCPMC9170159
OpenAlexW4225083529

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.